二十二碳六烯酸诱导细胞自噬减轻缺血性脑卒中神经损伤

被引：6

作者：

孙而艺 ^{[1
]}

张旋 ^{[2
]}

杨阳 ^{[2
]}

刘伟 ^{[2
]}

向欣 ^{[1
]}

冯华 ^{[2
]}

杨华 ^{[1
]}

机构：

[1] 贵州医科大学

[2] 第三军医大学西南医院神经外科

来源：

第三军医大学学报 | 2017年 / 39卷 / 14期

关键词：

二十二碳六烯酸; 缺血性脑卒中; 自噬; 神经功能保护;

D O I：

10.16016/j.1000-5404.201611242

中图分类号：

R743.3 [急性脑血管疾病（中风）];

学科分类号：

100204 [神经病学];

摘要：

目的探讨二十二碳六烯酸(docosahexaenoic acid,DHA)对大鼠缺血性脑卒中神经损伤的保护作用及其机制。方法利用60只280～330 g成年SD雄性大鼠建立永久性局灶脑梗死模型(permanent middle cerebral artery occlusion,pMCAO),按随机数字表法分为3组(n=20):假手术组、模型载体空白组(pMCAO+Veh)和模型DHA给药组(pMCAO+DHA)。建模成功后,按预设时间点对动物体质量、生存时间、神经功能、脑梗体积等大体指标进行评测;利用HE、Nissl染色对脑组织形态学改变进行观察;Western blot检测神经细胞自噬相关蛋白变化规律。结果造模后24、72 h,pMCAO+Veh组动物体质量及生存率较假手术组出现明显下降(P<0.05),DHA给药可明显改善上述指标,但差异无统计学意义(P>0.05);pMCAO+Veh组第7天生存率仅为38%,DHA早期干预可使第7天生存率提高至52%,但2组差异无统计学意义(P>0.05),DHA可明显改善由疾病模型造成的神经功能,包括认知、感觉、运动功能,从而获得更高的神经功能分数及更少的平衡木错失(P<0.05)。建模72 h后TTC染色发现,pMCAO+DHA组较pMCAO+Veh组可减少约17%的梗死体积(P<0.05);HE及Nissl染色发现,DHA给药可显著减轻皮层梗死区神经细胞的病理性损伤;Western blot蛋白检测,DHA可显著抑制梗死后mTOR表达(P<0.01),同时增强LC3Ⅰ/Ⅱ表达(P<0.05)。结论 DHA可显著减轻由缺血性脑卒中引起的病理性改变,其保护机制可能为负性调控mTOR通路作用从而激活自噬。

引用

页码：1452 / 1457

页数：6

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